Contribution of Cyclophilin A to determination of simian immunodeficiency virus tropism: a progress update

An understanding of cellular factors that affect viral replication contributes to elucidation of the mechanism for the determination of viral tropism. Cyclophilin A (CypA), a peptidyl-prolyl cis-trans isomerase (PPIase), is an essential host factor for the efficient replication of human immunodeficiency virus type 1 (HIV-1) in human cells. However, its role in simian immunodeficiency virus (SIV) replication has not been determined. In the 2008 US-Japan AIDS panel meeting, I have presented the effect of cyclosporine A (CsA), a PPIase inhibitor, on replication of wild-type SIV. Interestingly, CsA treatment enhanced SIV replication in human cells but abrogated SIV replication in macaque cells, implying a species-specific effect of CsA on SIV replication. After this meeting, analysis using CypA knocked-down human cells indicated that CypA was considered inhibitory for SIV replication. These results suggest possible involvement of CypA in the determination of SIV tropism.